{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:57:50Z","timestamp":1792270670545,"version":"4.4.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2020,3]]},"DOI":"10.1016\/j.jaci.2019.10.037","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T11:32:43Z","timestamp":1575286363000},"page":"808-817.e2","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":142,"title":["IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways"],"prefix":"10.1016","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-8615","authenticated-orcid":false,"given":"Martijn L.","family":"Manson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"S\u00e4fholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Karin","family":"Johnsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamdoh","family":"Al-Ameri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Charlotte","family":"Orre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"K\u00e4rrman-M\u00e5rdh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven-Erik","family":"Dahl\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Adner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaci.2019.10.037_bib1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.jaci.2006.07.012","article-title":"Mechanisms of airway hyperresponsiveness","volume":"118","author":"Cockcroft","year":"2006","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2019.10.037_bib2","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1164\/ajrccm\/142.4.832","article-title":"Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics","volume":"142","author":"Juniper","year":"1990","journal-title":"Am Rev Respir Dis"},{"key":"10.1016\/j.jaci.2019.10.037_bib3","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1164\/ajrccm.159.4.9806052","article-title":"Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group","volume":"159","author":"Sont","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib4","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/nm.2678","article-title":"Asthma phenotypes: the evolution from clinical to molecular approaches","volume":"18","author":"Wenzel","year":"2012","journal-title":"Nat Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib5","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","article-title":"Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma","volume":"378","author":"Castro","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib6","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.chest.2017.05.019","article-title":"New anti-eosinophil drugs for asthma and COPD: targeting the trait!","volume":"152","author":"Bel","year":"2017","journal-title":"Chest"},{"key":"10.1016\/j.jaci.2019.10.037_bib7","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1164\/rccm.201212-2318OC","article-title":"Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma","volume":"188","author":"Busse","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib8","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1183\/09031936.00112606","article-title":"Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma","volume":"29","author":"An","year":"2007","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2019.10.037_bib9","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/sj.bjp.0705558","article-title":"IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle","volume":"140","author":"Tliba","year":"2003","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2019.10.037_bib10","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1124\/mol.108.045419","article-title":"Interleukin 13 increases contractility of murine tracheal smooth muscle by a phosphoinositide 3-kinase p110delta-dependent mechanism","volume":"73","author":"Farghaly","year":"2008","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.jaci.2019.10.037_bib11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1165\/rcmb.2008-0162OC","article-title":"Interleukin-13 augments bronchial smooth muscle contractility with an up-regulation of RhoA protein","volume":"40","author":"Chiba","year":"2009","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jaci.2019.10.037_bib12","doi-asserted-by":"crossref","first-page":"L520","DOI":"10.1152\/ajplung.00343.2001","article-title":"IL-13-dependent autocrine signaling mediates altered responsiveness of IgE-sensitized airway smooth muscle","volume":"282","author":"Grunstein","year":"2002","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jaci.2019.10.037_bib13","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1067\/mai.2002.122459","article-title":"The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness","volume":"109","author":"Rizzo","year":"2002","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2019.10.037_bib14","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nm.2684","article-title":"IL-17A produced by alphabeta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction","volume":"18","author":"Kudo","year":"2012","journal-title":"Nat Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib15","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1111\/j.1365-2222.2004.02031.x","article-title":"Interleukin-4 increases murine airway response to kinins, via up-regulation of bradykinin B1-receptors and altered signalling along mitogen-activated protein kinase pathways","volume":"34","author":"Bryborn","year":"2004","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaci.2019.10.037_bib16","doi-asserted-by":"crossref","first-page":"L530","DOI":"10.1152\/ajplung.00133.2009","article-title":"TLR3 activation stimulates cytokine secretion without altering agonist-induced human small airway contraction or relaxation","volume":"297","author":"Cooper","year":"2009","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jaci.2019.10.037_bib17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.prostaglandins.2015.04.005","article-title":"Reversal of IL-13-induced inflammation and Ca(2+) sensitivity by resolvin and MAG-DHA in association with ASA in human bronchi","volume":"121","author":"Khaddaj-Mallat","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"10.1016\/j.jaci.2019.10.037_bib18","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1165\/rcmb.2015-0038OC","article-title":"IL-17RA signaling in airway inflammation and bronchial hyperreactivity in allergic asthma","volume":"53","author":"Willis","year":"2015","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jaci.2019.10.037_bib19","doi-asserted-by":"crossref","first-page":"e0207767","DOI":"10.1371\/journal.pone.0207767","article-title":"Human lung tissue provides highly relevant data about efficacy of new anti-asthmatic drugs","volume":"13","author":"Danov","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.jaci.2019.10.037_bib20","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/sj.bjp.0704928","article-title":"An assay to evaluate the long-term effects of inflammatory mediators on murine airway smooth muscle: evidence that TNFalpha up-regulates 5-HT(2A)-mediated contraction","volume":"137","author":"Adner","year":"2002","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2019.10.037_bib21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0014-2999(86)90080-4","article-title":"Human small airway smooth muscle responses in\u00a0vitro: actions and interactions of methacholine, histamine and leukotriene C4","volume":"125","author":"De Jongste","year":"1986","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.jaci.2019.10.037_bib22","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jaci.2019.04.031","article-title":"Mannitol triggers mast cell-dependent contractions of human small bronchi and prostacyclin bronchoprotection","volume":"144","author":"Safholm","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2019.10.037_bib23","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.jaci.2015.04.002","article-title":"Prostaglandin E2 inhibits mast cell-dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor","volume":"136","author":"Safholm","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2019.10.037_bib24","doi-asserted-by":"crossref","first-page":"L1121","DOI":"10.1152\/ajplung.00288.2015","article-title":"The TLR7 agonist imiquimod induces bronchodilation via a nonneuronal TLR7-independent mechanism: a possible role for quinoline in airway dilation","volume":"310","author":"Larsson","year":"2016","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jaci.2019.10.037_bib25","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1038\/sj.onc.1204629","article-title":"Induction of the IL-13 receptor alpha2-chain by IL-4 and IL-13 in human keratinocytes: involvement of STAT6, ERK and p38 MAPK pathways","volume":"20","author":"David","year":"2001","journal-title":"Oncogene"},{"key":"10.1016\/j.jaci.2019.10.037_bib26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nm1332","article-title":"IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis","volume":"12","author":"Fichtner-Feigl","year":"2006","journal-title":"Nat Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1164\/ajrccm.164.1.2008060","article-title":"Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells","volume":"164","author":"Laporte","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib28","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.bmc.2006.10.015","article-title":"Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors","volume":"15","author":"Nagashima","year":"2007","journal-title":"Bioorg Med Chem"},{"key":"10.1016\/j.jaci.2019.10.037_bib29","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jaci.2012.12.1567","article-title":"Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: a systematic review","volume":"131","author":"van der Wiel","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2019.10.037_bib30","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1183\/09031936.00170912","article-title":"Small airways in asthma: their independent contribution to the severity of hyperresponsiveness","volume":"41","author":"Telenga","year":"2013","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2019.10.037_bib31","first-page":"299","article-title":"Nifedipine inhibits human bronchial smooth muscle contractions induced by leukotrienes C4 and D4, prostaglandin F2 alpha, and potassium","volume":"132","author":"Kohrogi","year":"1985","journal-title":"Am Rev Respir Dis"},{"key":"10.1016\/j.jaci.2019.10.037_bib32","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/0091-6749(89)90356-4","article-title":"Sensitization alters contractile responses and calcium influx in human airway smooth muscle","volume":"84","author":"Black","year":"1989","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2019.10.037_bib33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1476-5381.1986.tb09468.x","article-title":"Effects of Bay K 8644 on contraction of the human isolated bronchus and guinea-pig isolated trachea","volume":"88","author":"Advenier","year":"1986","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2019.10.037_bib34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1183\/09059180.00010410","article-title":"The role of small airways in obstructive airway diseases","volume":"20","author":"Burgel","year":"2011","journal-title":"Eur Respir Rev"},{"key":"10.1016\/j.jaci.2019.10.037_bib35","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1165\/rcmb.2003-0313OC","article-title":"Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: role of CD38\/cyclic adenosine diphosphate ribose pathway","volume":"31","author":"Deshpande","year":"2004","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jaci.2019.10.037_bib36","doi-asserted-by":"crossref","first-page":"L171","DOI":"10.1152\/ajplung.00457.2007","article-title":"MAP kinases mediate interleukin-13 effects on calcium signaling in human airway smooth muscle cells","volume":"295","author":"Moynihan","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jaci.2019.10.037_bib37","doi-asserted-by":"crossref","first-page":"L958","DOI":"10.1152\/ajplung.00247.2010","article-title":"Interleukin-13 inhibits proliferation and enhances contractility of human airway smooth muscle cells without change in contractile phenotype","volume":"300","author":"Risse","year":"2011","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.jaci.2019.10.037_bib38","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1067\/mai.2003.1451","article-title":"CysLT1 receptor upregulation by TGF-beta and IL-13 is associated with bronchial smooth muscle cell proliferation in response to LTD4","volume":"111","author":"Espinosa","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2019.10.037_bib39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1098\/rspb.1983.0093","article-title":"Operational models of pharmacological agonism","volume":"220","author":"Black","year":"1983","journal-title":"Proc R Soc Lond B Biol Sci"},{"key":"10.1016\/j.jaci.2019.10.037_bib40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1476-5381.2010.01199.x","article-title":"Glucocorticosteroids: current and future directions","volume":"163","author":"Barnes","year":"2011","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2019.10.037_bib41","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1183\/09059180.00007609","article-title":"Investigational therapeutics targeting the IL-4\/IL-13\/STAT-6 pathway for the treatment of asthma","volume":"19","author":"Oh","year":"2010","journal-title":"Eur Respir Rev"},{"key":"10.1016\/j.jaci.2019.10.037_bib42","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1006\/jmbi.2001.4765","article-title":"Solution structure of interleukin-13 and insights into receptor engagement","volume":"310","author":"Eisenmesser","year":"2001","journal-title":"J Mol Biol"},{"key":"10.1016\/j.jaci.2019.10.037_bib43","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1056\/NEJMoa1804093","article-title":"Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma","volume":"378","author":"Rabe","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib44","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S2213-2600(16)30265-X","article-title":"Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials","volume":"4","author":"Hanania","year":"2016","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib45","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S2213-2600(18)30184-X","article-title":"Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials","volume":"6","author":"Panettieri","year":"2018","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.jaci.2019.10.037_bib46","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00936-2018","article-title":"Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma","volume":"52","author":"Bleecker","year":"2018","journal-title":"Eur Respir J"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674919316185?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674919316185?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:25:10Z","timestamp":1758792310000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091674919316185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["S0091674919316185"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2019.10.037","relation":{},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2019.10.037","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.","name":"copyright","label":"Copyright"}]}}